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Titanium dioxide nanoparticles (TiO2 NPs) have been used in various medical and industrial areas. However, the impacts of these nanoparticles on neuroinflammation in the brain are poorly understood. In this study, mice were exposed to 2.5, 5, or 10 mg/kg body weight TiO2 NPs for 90 consecutive days, and the TLRs/TNF-α/NF-κB signaling pathway associated with the hippocampal neuroinflammation was investigated. Our findings showed titanium accumulation in the hippocampus, neuroinflammation and impairment of spatial memory in mice following exposure to TiO2 NPs. Furthermore, TiO2 NPs significantly activated the expression of Toll-like receptors (TLR2, TLR4), tumor necrosis factor-α, nucleic IκB kinase, NF-κB-inducible kinase, nucleic factor–κB, NF-κB2(p52), RelA(p65), and significantly suppressed the expression of IκB and interleukin-2. These findings suggest that neuroinflammation may be involved in TiO2 NP-induced alterations of cytokine expression in mouse hippocampus. Therefore, more attention should be focused on the application of TiO2 NPs in the food industry and their long-term exposure effects, especially in the human central nervous system. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated nanosized titanium dioxide (nano-TiO2)-induced fertility reduction and ovary injury in animals. To better understand how nano-TiO2 act in mice, female mice were exposed to 2.5, 5, and 10 mg/kg nano-TiO2 by intragastric administration for 90 consecutive days; the ovary injuries, fertility, hormone levels, and inflammation-related or follicular atresia-related cytokine expression were investigated. The results showed that nano-TiO2 was deposited in the ovary, resulting in significant reduction of body weight, relative weight of ovary and fertility, alterations of hematological and serum parameters and sex hormone levels, atretic follicle increases, inflammation, and necrosis. Furthermore, nano-TiO2 exposure resulted in marked increases of insulin-like growth factor-binding protein 2, epidermal growth factor, tumor necrosis factor-α, tissue plasminogen activator, interleukin-1β, interleukin -6, Fas, and FasL expression, and significant decreases of insulin-like growth factor-1, luteinizing hormone receptor, inhibin α, and growth differentiation factor 9 expression in mouse ovary. These findings implied that fertility reduction and ovary injury of mice following exposure to nano-TiO2 may be associated with alteration of inflammation-related or follicular atresia-related cytokine expressions, and humans should take great caution when handling nano-TiO2. [ABSTRACT FROM AUTHOR]

Background: Nanoparticulate titanium dioxide (nano-TiO 2 ) enters the body through various routes and causes organ damage. Exposure to nano-TiO 2 is reported to cause testicular injury in mice or rats and decrease testosterone synthesis, sperm number, and motility. Importantly, nano-TiO 2 suppresses testosterone production by Leydig cells (LCs) and impairs the reproductive capacity of animals., Methods: In an attempt to establish the molecular mechanisms underlying the inhibitory effect of nano-TiO 2 on testosterone synthesis, primary cultured rat LCs were exposed to varying concentrations of nano-TiO 2 (0, 10, 20, and 40 µg/mL) for 24 hours, and alterations in cell viability, cell injury, testosterone production, testosterone-related factors (StAR, 3βHSD, P450scc, SR-BI, and DAX1), and signaling molecules (ERK1/2, PKA, and PKC) were investigated., Results: The data show that nano-TiO 2 crosses the membrane into the cytoplasm or nucleus, triggering cellular vacuolization and nuclear condensation. LC viability decreased in a time-dependent manner at the same nano-TiO 2 concentration, nano-TiO 2 treatment (10, 20, and 40 µg/mL) decreased MMP (36.13%, 45.26%, and 79.63%), testosterone levels (11.40% and 44.93%), StAR (14.7%, 44.11%, and 72.05%), 3βHSD (26.56%, 50%, and 79.69%), pERK1/2 (27.83%, 63.61%, and 78.89%), PKA (47.26%, 70.54%, and 85.61%), PKC (30%, 50%, and 71%), SR-BI (16.41%, 41.79%, and 67.16%), and P450scc (39.41%, 55.26%, and 86.84%), and upregulated DAX1 (1.31-, 1.63-, and 3.18-fold) in primary cultured rat LCs., Conclusion: Our collective findings indicated that nano-TiO 2 -mediated suppression of testosterone in LCs was associated with regulation of ERK1/2-PKA-PKC signaling pathways., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Numerous studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) induced nephrotoxicity in animals. However, the nephrotoxic multiple molecular mechanisms are not clearly understood., Methods: Mice were exposed to 2.5, 5 and 10 mg/kg TiO2 NPs by intragastric administration for 90 consecutive days, and their growth, element distribution, and oxidative stress in kidney as well as kidney gene expression profile were investigated using whole-genome microarray analysis technique., Results: Our findings suggest that TiO2 NPs resulted in significant reduction of renal glomerulus number, apoptosis, infiltration of inflammatory cells, tissue necrosis or disorganization of renal tubules, coupled with decreased body weight, increased kidney indices, unbalance of element distribution, production of reactive oxygen species and peroxidation of lipid, protein and DNA in mouse kidney tissue. Furthermore, microarray analysis showed significant alterations in the expression of 1, 246 genes in the 10 mg/kg TiO2 NPs-exposed kidney. Of the genes altered, 1006 genes were associated with immune/inflammatory responses, apoptosis, biological processes, oxidative stress, ion transport, metabolic processes, the cell cycle, signal transduction, cell component, transcription, translation and cell differentiation, respectively. Specifically, the vital up-regulation of Bcl6, Cfi and Cfd caused immune/ inflammatory responses, the significant alterations of Axud1, Cyp4a12a, Cyp4a12b, Cyp4a14, and Cyp2d9 expression resulted in severe oxidative stress, and great suppression of Birc5, Crap2, and Tfrc expression led to renal cell apoptosis., Conclusions: Axud1, Bcl6, Cf1, Cfd, Cyp4a12a, Cyp4a12b, Cyp2d9, Birc5, Crap2, and Tfrc may be potential biomarkers of kidney toxicity caused by TiO2 NPs exposure.